Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial

PLOS ONE, Dec 2019

Background In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking. Objective The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function. Design This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25) and women (n = 20) with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period. Results Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791), apoB100; -0.01 ± 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721), LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687), glucose; -0.08 ± 0.28 mmol/L (P = 0.064), insulin; -0.3 ± 2.5 mU/L (P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed. Conclusion 150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study. Trial Registration ClinicalTrials.gov NCT01364961

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Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial

March Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial Sanne M. van der Made 0 1 Jogchum Plat 0 1 Ronald P. Mensink 0 1 0 1 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center , Maastricht , The Netherlands , 2 Top Institute of Food and Nutrition (TIFN) , Wageningen , The Netherlands 1 Academic Editor: Giuseppe Danilo Norata, University of Milan , ITALY - Funding: The project is funded by TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition. The public partners are responsible for the study design, data collection and analysis, decision to publish, and preparation of the manuscript. Trans-resveratrol In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking. The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function. This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25) and women (n = 20) with a mean age of 61 7 years. Subjects received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period. Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 0.12 g/L (P = 0.791), apoB100; -0.01 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 0.09 mmol/L capsules were provided by DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland). Competing Interests: The funding we received from TI Food and Nutrition and the capsules that were given by DSM Nutritional Products Ltd. does not alter the authors adherence to PLOS ONE policies on sharing data and materials. (P = 0.721), LDL cholesterol -0.03 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 0.54 mmol/L (P = 0.687), glucose; -0.08 0.28 mmol/L (P = 0.064), insulin; -0.3 2.5 mU/L (P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed. 150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study. ClinicalTrials.gov NCT01364961 The many approaches that exist to lower cardiovascular risk are mainly aimed at lowering LDL cholesterol concentrations. Based on epidemiological studies [14], increasing HDL cholesterol concentrations may also reduce cardiovascular risk, but this concept has been challenged by intervention studies [57]. However, a recent meta-analysis has suggested that increasing apolipoprotein A-I (apoA-I) concentrations is a more important target to reduce the risk of major cardiovascular events than increasing HDL cholesterol concentrations [8]. ApoA-I is the major protein constituent of the HDL particle, which plays a crucial role in many of the favorable effects attributed to HDL particles, includingnext to their fundamental role in reverse cholesterol transportanti-inflammatory, anti-thrombotic and anti-oxidative effects [9,10]. Epidemiological studies have shown a positive association between higher polyphenol intakes and reduced cardiovascular risk [11,12]. This association may be due to increased intakes of trans-resveratrol (3,5,4-trihydroxystilbene), a polyphenol found in the skin of black grapes. Resveratrol may influence numerous mechanisms, which act on the progression as well as on the regression of atherosclerosis [13]. In fact, in vitro and animal studies have shown many positive effects of resveratrol on genes and proteins involved in lipid and glucose metabolism, including increases in the activities of peroxisome proliferator-activated receptor (PPAR) and PPAR [14,15]. While the results from in vitro and animal studies are promising, and an HDL cholesterol elevating effect of berries [16] and red wine [17], both of which contain resveratrol, has been reported, human studies with the primary aim to examine the effects of resveratrol on lipid and lipoprotein metabolism are scarce. Furthermore, human data onto the effect of resveratrol on markers for metabolic risk is limited an (...truncated)


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Sanne M. van der Made, Jogchum Plat, Ronald P. Mensink. Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial, PLOS ONE, 2015, Volume 10, Issue 3, DOI: 10.1371/journal.pone.0118393